P772: PROGNOSTIC IMPACT OF DISEASE-RELATED RISK FACTORS AND TREATMENT APPROACHES IN PATIENTS WITH ADVANCED MYELODYSPLASTIC SYNDROMES (MDS)
Authors: C. Lesch, A. Kündgen, K. Nachtkamp, A. Kasprzak, C. Strupp, M. Rudelius, N. Gattermann, G. Kobbe, B. Hildebrandt, U. Germing
Journal: HemaSphere (2022)

Background: Myelodysplastic syndromes (MDS) are heterogeneous hematopoietic stem cell disorders. Treatment approaches depend on the type of MDS according to the WHO classification and on risk assessment according to the international prognostic scoring system (IPSS-R). For patients with advanced MDS, as defined by an excess of blasts, therapeutic options include hypomethylating agents and allogeneic stem cell transplantation. Aims: To determine the prognostic impact of disease-related risk factors and treatment approaches in 432 patients with MDS EB1 and EB2. Methods: Patients included in this analysis were classified as having MDS EB1 (5-9% marrow blasts) or MDS EB2 (10-19% marrow blasts) at diagnosis. All therapeutic procedures prior to the development of acute myeloid leukemia (AML) were documented. Patients were followed up until 31st December 2021, or until death. Therapeutic approaches were categorized as best supportive care (BSC) only, low-dose chemotherapy, immunomodulatory treatment, hypomethylating agents (HMA), intensive chemotherapy (IC) and allogeneic stem cell transplantation (alloSCT). The mentioned therapy regimes were weighted in different categories according to their intensity, with BSC defined as the therapy with the lowest intensity and alloSCT as the one with the highest (BSC < low-dose-chemotherapy < immunomodulatory treatment < HMA < IC < allo SCT). Results: MDS EB1 was diagnosed in 182 patients (42,1%), and MDS EB2 in 250 patients (57,9%). Distribution among IPSS-R risk groups was as follows: 2% low risk, 26.3% intermediate risk, 38% high risk, and 33,7% very high risk. Median life expectancy in the entire cohort including patients with all types of treatment, was 22 months. Progression to AML occurred in 186 (43%) of the patients. Patients receiving supportive care only (42.6%) had a median survival of 13 months. Patients treated with a hypomethylating agent (18%) showed an overall survival of 26 months, which was significantly better compared with best supportive care (p=0.002). Patients undergoing induction chemotherapy (6%) had a median survival of 21 months, comparable with HMA treatment. Patients receiving low-dose chemotherapy (4.6%) had a median survival of 9 months. The longest median survival (131 months) was seen in patients undergoing alloSCT. Multivariate Cox regression analysis showed that treatment category (p<0.00005), together with cytogenetic risk category according to IPSS-R (very low, low and intermediate versus high versus very high) (p<0.0005), and hemoglobin (<≥10g/dl) (p=0.003) were the only parameters influencing survival independently, whereas WHO type, gender, ANC, and platelets did not show independent influence on survival. Summary/Conclusion: Stratification according to cytogenetic risk groups is very important for the prognostic assessment of MDS patients. Assignment to the cytogenetic group high risk and very high risk has greater prognostic impact than the medullary blast count. Even though hypomethylating agents can improve overall survival compared to best supportive care, long-term survival can only be achieved through allogeneic stem cell transplantation. Therefore, all patients eligible for intensive treatment should be evaluated for this treatment option at the time of diagnosis. Furthermore, in recognition of the fact that clonal evolution may occur in MDS patients, consideration should be given to repeating the chromosome analysis as the most important prognostic factor at regular intervals.